Key Pancreatic Cancer Defect Is Identified by UCSF Researchers

Pancreatic cancer, compared to other types of leading cancer killers, is detected later and does not respond well to either new or established drugs. Now a new UC San Francisco study has shed light on the origins of one type of deadly pancreatic cancer.

In a study published online February 23, 2014 in the journal Nature Cell Biology, researchers led by Matthias Hebrok, PhD, head of the UCSF Diabetes Center, reported the identification of a key gene that normally holds tumor development at bay but, when damaged by mutation, allows pancreatic tumors to develop.

Absent advances that could lead to earlier diagnosis and better treatment, only about 6 percent of those in the United States who are diagnosed with pancreatic cancer will be alive five years from now, according to a National Cancer Institute prediction. In the United States, pancreatic cancer receives little press but now kills nearly as many as breast cancer. The American Cancer Society estimates that 40,430 will die of breast cancer in 2014, while 39,590 will die of pancreatic cancer.

In their latest study, the UCSF researchers used a new mouse model they bred especially to explore a mutated gene, called Brg1, or SMARCA4 in humans. They found that loss of the protein encoded by the gene – a result of genetic mutation – helps to trigger development of a type of pancreatic cancer thought to arise from cells lining the digestive-enzyme-secreting ducts of the pancreas.

Rapid advances in scientists’ ability to unravel genomes of both tumors and normal tissues have led to the discovery of many genes that are abnormal in certain cancers. However, not all of these abnormal mutations in cancer drive tumor growth, and the biological importance of many of these mutated genes awaits study in cells grown in the lab or in animal models.

Previous studies of pancreatic cancer often have focused on the role of a mutated protein called K-ras. K-ras is implicated in almost all cases of pancreatic cancer and is common in many other cancers. K-Ras has so far been notoriously difficult to target with new drugs, although UCSF researchers led by Kevan Shokat, PhD, recently identified a promising K-ras targeting strategy.